12-111774029-T-C

Variant names:

• chr12-111774029-T-C
• rs2238151
• NM_000690.4:c.114+6933T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000690.4(ALDH2):​c.114+6933T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.525 in 152,120 control chromosomes in the GnomAD database, including 26,032 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.53 (26032 hom., cov: 32)
• Consequence: ALDH2 NM_000690.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.905
• Publications: 63 publications found

Genes affected

ALDH2 (HGNC:404): (aldehyde dehydrogenase 2 family member) This protein belongs to the aldehyde dehydrogenase family of proteins. Aldehyde dehydrogenase is the second enzyme of the major oxidative pathway of alcohol metabolism. Two major liver isoforms of aldehyde dehydrogenase, cytosolic and mitochondrial, can be distinguished by their electrophoretic mobilities, kinetic properties, and subcellular localizations. Most Caucasians have two major isozymes, while approximately 50% of East Asians have the cytosolic isozyme but not the mitochondrial isozyme. A remarkably higher frequency of acute alcohol intoxication among East Asians than among Caucasians could be related to the absence of a catalytically active form of the mitochondrial isozyme. The increased exposure to acetaldehyde in individuals with the catalytically inactive form may also confer greater susceptibility to many types of cancer. This gene encodes a mitochondrial isoform, which has a low Km for acetaldehydes, and is localized in mitochondrial matrix. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Nov 2016]

ENSG00000257767 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.922 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000690.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH2	NM_000690.4	MANE Select	c.114+6933T>C		intron	N/A	NP_000681.2
	ALDH2	NM_001204889.2		c.114+6933T>C		intron	N/A	NP_001191818.1	P05091-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH2	ENST00000261733.7	TSL:1 MANE Select	c.114+6933T>C		intron	N/A	ENSP00000261733.2	P05091-1
	ENSG00000257767	ENST00000546840.3	TSL:5	c.103-7889T>C		intron	N/A	ENSP00000450353.4	F8VP50
	ALDH2	ENST00000871406.1		c.115-1581T>C		intron	N/A	ENSP00000541465.1

Frequencies

GnomAD3 genomes AF: 0.525 AC: 79794 AN: 152002 Hom.: 25980 Cov.: 32

Gnomad AFR AF: 0.881

Gnomad AMI AF: 0.414

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.197

Gnomad EAS AF: 0.944

Gnomad SAS AF: 0.691

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.324

Gnomad OTH AF: 0.483

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.525 AC: 79908 AN: 152120 Hom.: 26032 Cov.: 32 AF XY: 0.532 AC XY: 39562 AN XY: 74362

African (AFR) AF: 0.882 AC: 36606 AN: 41524

American (AMR) AF: 0.473 AC: 7234 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 684 AN: 3466

East Asian (EAS) AF: 0.944 AC: 4891 AN: 5182

South Asian (SAS) AF: 0.691 AC: 3330 AN: 4818

European-Finnish (FIN) AF: 0.342 AC: 3612 AN: 10552

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.324 AC: 22004 AN: 67982

Other (OTH) AF: 0.482 AC: 1018 AN: 2114

Alfa AF: 0.395 Hom.: 42078

Bravo AF: 0.550

Asia WGS AF: 0.764 AC: 2655 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.7
DANN	Benign	0.46
PhyloP100		-0.91
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2238151; hg19: chr12-112211833;